The present invention relates generally to ophthalmic compositions. In particular, the present invention relates to the use of certain vitamin E tocopheryl derivatives to provide comfortable, non-irritating ophthalmic compositions. In addition, the present invention relates to the use of these vitamin E tocopheryl derivatives to increase the solubility of poorly soluble ophthalmic agents in aqueous compositions. For purposes of the present specification, the vitamin E tocopheryl derivatives useful in the present invention shall be referred to as "vitamin E tocopheryl derivatives" or "vitamin E derivatives" or "TPGS."
Stinging and burning sensations, as well as general discomfort, are often associated with the topical ophthalmic application of certain types of ophthalmic agents. It is believed that such ocular discomfort is due to the presence of certain functional groups in these agents. Examples of such agents which produce ocular discomfort include, but are not limited to:.beta.-blockers such as betaxolol; prostaglandins and prostaglandin derivatives; muscarinics such as pilocarpine; .alpha.-adrenergics such as epinephrine, clonidine and apraclonidine; cholinergics such as carbachol; and non-steroidal anti-inflammatory drugs ("NSAIDs") such as diclofenac and suprofen.
There have been a number of attempts to formulate topical ophthalmic compositions to reduce the inherent discomfort associated with these ophthalmic agents. Such attempts include those described in U.S. Pat. No. 4,559,343 (Han et al.), U.S. Pat. No. 4,911,920 (Jani et al.), U.S. Pat. No. 5,093,126 (Jani et al.), and U.S. Pat. No. 5,212,162 (Missel et al.). Han et al. describe the addition of xanthine derivatives, such as caffeine, to decrease the stinging associated with topical ocular application of NSAIDs. The two Jani et al. references teach the addition of certain ion-exchange resins to compositions of .beta.-blockers to increase comfort and to provide sustained release. Missel et al. teach combinations of gelling polysaccharides and finely-divided drug carrier substrates ("DCS") which provide comfortable and sustained release ophthalmic compositions.
In addition, U.S. Pat. No. 4,960,799 (Nagy), discloses storage stable aqueous ophthalmic compositions containing diclofenac and/or its pharmaceutically acceptable salts. The Nagy compositions include EDTA and a solubilizer such as ethoxylated castor oil.